The ambitious goal of this volume is to provide in chapters written by accomplished scientists and experts in their field a comprehensive overview of the currently available information related to the therapeutic utility of adult bone marrow-derived cells. With excitement generated almost daily about the possible uses of stem cells to treat human disease, but the controversy surrounding their use still raging, adult bone-marrow derived cells are more readily available, and have a staggering range of uses.

In light of the rising cost of healthcare and the overall challenges associated with delivering quality care to patients across regions, scientists and pharmacists are exploring new initiatives in drug discovery and design. One such initiative is the adoption of information technology and software applications to improve healthcare and pharmaceutical processes. Software Innovations in Clinical Drug Development and Safety is a comprehensive resource analyzing the integration of software engineering for the purpose of drug discovery, clinical trials, genomics, and drug safety testing. Taking a multi-faceted approach to the application of computational methods to pharmaceutical science, this publication is ideal for healthcare professionals, pharmacists, computer scientists, researchers, and students seeking the latest information on the architecture and design of software in clinical settings, the impact of clinical technologies on business models, and the safety and privacy of patients and patient data. This timely resource features a well-rounded discussion on topics pertaining to the integration of computational methods in pharmaceutical science and practice including, the impact of software integration on business models, patient safety concerns, software architecture and design, and data security.

This textbook provides a comprehensive overview of the currently used concepts, approaches and technologies in the discovery and development of new treatments for the full spectrum of disorders of the central nervous system. It guides the reader through all essential steps, from finding an innovative idea, to the registration of a new drug. Divided into four sections, the book starts by presenting a broad perspective on current approaches in central nervous system (CNS) drug discovery. The second section addresses the generation of ideas for the identification of targets and novel treatment strategies; covers core functions in early discovery, and provides an example of a novel treatment paradigm: brain stimulation. The third section highlights strategies and technologies in translational CNS drug discovery. In an effort to bridge the gap between discovery and clinical development, it also covers brain imaging, EEG and cognitive testing approaches. The fourth section extensively discusses the clinical phase of drug development, covering the basics of early clinical testing for psychopharmacological drugs. The book's final chapter addresses the registration for newly developed drugs. Written by experts from academia and industry, the book covers important basics and best practices, as well as recent developments in drug discovery. Offering in-depth insights into the world of drug development, it represents essential reading for early researchers who want to prepare for a career in drug discovery in academia or industry.

The world's population is growing at an unsustainable rate. From a baseline ?gure of one billion in 1800, global population is predicted to exceed nine billion by 2050 and 87. 8% of this growth will be localized in less developed countries. Such uneven population growth will yield a harvest of poverty, malnutrition, disease and en- ronmental degradation that will affect us all. Amongst the complex mixture of political, social, cultural and technological changes needed to address this issue, the development of improved methods of fertility regulation will be critical. The inadequacy of current contraceptive technologies is indicated by recent data s- gesting that the contraceptive needs of over 120 million couples go unmet every year. As a direct consequence of this de?cit 38% of pregnancies are unplanned and more than 50% end in an abortion, generating a total of 46 million abortions per annum particularly among teenagers. If safe, effective contraceptives were ava- able to every couple experiencing an unmet family planning need, 1. 5 million lives would be saved each year (UNFPA 2003). Progress in contraceptive technology should not only generate more effective methods of regulating fertility, but should also provide a range of methods to meet the changing needs of the world's population. Contraceptive practice was revo- tionized in 1960 in the US and 1961 in Europe by the introduction of the oral contraceptive pill by Gregory Pincus, MC Chang and colleagues, based on fun- mental hormone research conducted in Germany.

Pharmacogenomics supports personalized medicine by translating genome-based knowledge into clinical practice, offering enhanced benefit for patients and health-care systems at large. Current routine practice for diagnosing and treating patients is conducted by correlating parameters such as age, gender and weight with risks and expected treatment outcomes. In the new era of personalized medicine the healthcare provider is equipped with improved ability to prevent, diagnose, treat and predict outcomes on the basis of complex information sources, including genetic and genomic data. Targeted therapy and reliable prediction of expected outcomes offer patients access to better healthcare management, by way of identifying the therapies effective for the relevant patient group, avoiding prescription of unnecessary treatment and reducing the likelihood of developing adverse drug reactions.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Natural products play an integral and ongoing role in promoting numerous aspects of scientific advancement, and many aspects of basic research programs are intimately related to natural products. The significance, therefore, of the Studies in Natural Product Chemistry series, edited by Professor Atta-ur-Rahman, cannot be overestimated. This volume, in accordance with previous volumes, presents us with cutting-edge contributions of great importance.

The reader will be introduced to various aspects of the fundamentals of nanotechnology based drug delivery systems and the application of these systems for the delivery of small molecules, proteins, peptides, oligonucleotides and genes. How these systems overcome challenges offered by biological barriers to drug absorption and drug targeting will also be described.

The majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

This monograph contains a description of the discovery and development of a antisecretory therapy in the treatment of acid-related diseases: omeprazole, the first proton pump inhibitor. Overviews compare this and other proton pump inhibitors and discuss their pharmacology, including the mechanism of action, the effect on Helicobacter pylori infection, and the consequences of profound inhibition of gastric acid secretion. The pharmaceutic delivery system is described since it constitutes a special problem with this class of drugs. The clinical experience with proton pump inhibitors in acid-related diseases is reviewed with focus on gastro-esophageal reflux disease and peptic ulcer diseases including Helicobacter pylori and NSAID-induced ulcerations and Zollinger-Ellison syndrome. Finally, an overview is presented on the socio-economic impact of proton pump inhibitors in acid-related diseases emphasizing the important aspect of quality of life. The monograph is aimed at a broad readership with an interest in the development problems of this, at present, most commercially successful drug; the pharmacology of a "tailor-made" drug for a specific target; the therapeutic strategies in acid-related diseases; and the dramatic changes in the long-term outcome results of the treatment of peptic ulcer diseases where most patients now can be cured from the disease after only one week of drug therapy.

This book continues as volume 5 of a multicompendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh, cooked or processed as vegetables, cereals, spices, stimulant, edible oils and beverages. It covers selected species from the following families: Apiaceae, Brassicaceae, Chenopodiaceae, Cunoniaceae, Lythraceae, Papaveraceae, Poaceae, Polygalaceae, Polygonaceae, Proteaceae, Ranunculaceae, Rhamnaceae, Rubiaceae, Salicaceae, Santalaceae, Xanthorrhoeaceae and Zingiberaceae. This work will be of significant interest to scientists, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, botanists, agriculturists, conservationists, lecturers, students and the general public. Topics covered include: taxonomy; common/English and vernacular names; origin and distribution; agroecology; edible plant parts and uses; botany; nutritive/pharmacological properties, medicinal uses, nonedible uses; and selected references.

Because progress in the field of transporters has been extraordinary, this volume will focus on recent advances in our understanding of the structure, function, physiology, and molecular biology of membrane transporters. There will be an emphasis on transporters as molecular targets for drug delivery and disposition in the body.

Phytochemicals are components acting individually, additively or synergistically, usually as a component of whole food, that have the characteristics of providing protective, preventative and possibly curative roles in the pathogenesis of cancer and other chronic disease progressions. Nutraceutical is a term used to describe beneficial phytochemicals. The mechanisms of action of nutraceuticals may be one of several. Free radical scavenger and antioxidant nutraceuticals can nullify damage by any number of biochemical mechanisms, but some also exert benefit by enhancing immune function.

A conservative economic analysis was done in 1993 of solely hospital care costs and the roles that three nutrient antioxidants could exert on cardiovascular disease, breast cancer and cataracts. The study considered the potential impact of only three antioxidants, vitamins C and E, and beta-carotene, and the possible annual savings in hospital care costs alone, which could exceed 8 billion dollars. Expert public health physicians believe that as much as 700f disease is preventable.

The chapters in this book were organized to reveal existing and emerging knowledge of nutraceuticals found in garlic, soy and licorice. Lead chapters discuss the epidemiological evidence, and following chapters discuss chemical or biochemical evidence at the cellular level, as well as the presentation of some clinical data.

A major conclusion of the overall effort is that the science of nutraceuticals is very incomplete, but that findings to date have great promise.

The over-arching goal of this volume is to help infertility practitioners evaluate and manage their patients with poor semen quality. The authors review the existing literature on the effects of medications on male fertility, and provide detailed information about what is known, giving the number of individuals and population characteristics for studies of medication effects on male fertility. Medications are designed to treat illness and reduce symptoms, but all have undesirable adverse effects such as headache or stomach upset. Some adverse reactions can even be life-threatening, so it is no surprise that some drugs have negative effects on male reproduction. Medical practitioners rarely consider a man's reproductive plans when prescribing medications. Men are routinely treated with drugs that can impair or abolish fertility. Although practitioners in the field of reproductive medicine generally realize that certain drugs impact negatively on reproductive health, there are limited resources providing evidence-based knowledge useful in counseling patients. Tables throughout this volume summarize the information for each drug, providing a handy reference for clinical use.

This book is an essential handbook on bisphosphonates, the most widely used new class of drugs for osteoporosis therapy. It reviews basic physiology in addition to the indications and adverse reactions of these drugs. Bisphosphonates in Bone Disease, 4E, discusses the compounds' chemistry, mechanisms of action, and animal toxicology before presenting a clinical picture of the diseases treated by bisphosphonates. The book provides a table listing the trade names of the commercially available bisphosphonates, registered indications, and the available forms for various countries. The revised Fourth Edition contains approximately 50% new material, including information on all of the latest drugs.
* The revised fourth edition contains approximately 50% new material
* Includes information on all the latest drugs

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

Volume 3 of "Advances in Antiviral Drug Design" is keeping up with the recent progress made in the field of antiviral drug research and highlights five specific directions that have opened new avenues for the treatment of virus infections.
"First," the use of lamivudine (3TC) for the treatment of HIV infections, and its more recent introduction for the treatment of hepatitis B virus (HBV) infections, has heralded the transition of D- to L-nucleosides in the antiviral nucleoside drug design, and it is likely that the future will provide more nucleosides of the L-configuration, such as (-)FFC (emtricitabine) and L-FMAU, as will be described by J.-C.G. Graciet and R.F. Shinazi.
"Second," the acyclic purine nucleoside phosphonates, i.e. PMEA (adefovir and PMPA (tenofovir), offer great potential as both anti-HIV and anti-HBV agents, and both compounds have been the subject of advanced clinical trials in their oral produrg form (adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N. Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger.
"Third," with the advent of nevirapine, delavirdine, and efavirenz, the NNRTIs have definitely come of age. Emivirine (MKC-442), a derivative of the original HEPT analog that was described in 1989 has now proceeded through pivotal clinical studies, and how this class of compounds evolved is presented in the account of H. Tanaka and his colleagues.
"Fourth," at the end of 1999, anticipating on the next winter influenza offensive, we should have at end two compounds that specifically inhibit influenza A and B virus infections: zanamivir (by the intranasal route) and oseltamivir (by the oral route). Both compounds have proved effective in the prophylaxis and treatment of influenza A and B virus infections and act through the same mechanism; that is by blocking the viral neuraminidase (or sialidase), a key enzyme that allows the virus to spread from one cell to another (within the respiratory mucosal tract). The design of these sialidase inhibitors will be presented by M. von Itzstein and J.C. Dyason.
"Fifth," the discovery (in 1996) of the chemokine receptors CXCR4 and CCR5 as essential coreceptors (in addition to the CD4 receptor) for HIV entry into the cells, has boosted an enormous interest in potential antagonists of these receptors. The bicyclams represent the first low-molecular-weight compounds targeted at CXCR4, the coreceptor used by the more pathogenic, T-lymphotropic, HIV strains, to enter the cells. They will be addressed by G.J. Bridger and R.T. Skerlj.
The five topics covered in this third volume of "Advances in" "Antiviral Drug Design" are in the front line of the present endeavors towards the chemotherapy of virus infections. They pertain to the combat against three of the most important virus infections of current times: HIV, HBV, and influenza virus.

This book introduces some emerging functional foods that are natural resources with tremendous promise as nutraceuticals and pharmaceuticals. The author considers biodiversity and bioprospecting as a response to food security issues, drug-resistance, nutrition-poor diets and other problems, exploring the prospects of several under-utilized nutrients and bioactive repositories. Readers will discover biochemical makeups, validated health benefits, explanations of underlying mechanisms, hurdles in the path of popularity and promotion strategies. Chapters explore particular plants, seeds and fruits including the strawberry guava, opuntia fruits, the Carissa genus, grape seeds, quinoa and the milk thistle (Silybum), amongst others. They are considered as food sources where possible and from the perspective of the roles they can play in complementary and alternative medicine, such as in wound healing, antimicrobial activity, gastroprotective activity in treatment of cancers and as natural antioxidant sources. This rich compilation holds plausible solutions to a range of current issues and it endorses the much-needed goal of sustainability in terms of diet and drugs. It paves the path for further research and development on hitherto obscure natural resources. Scientists working in the area of food development, phytochemical and antioxidant analysis, bioprospecting of low-profile foods and in complementary and alternative medicine will find this work particularly valuable. It will also be of interest to the general reader with an interest in food science, food security, phytochemicals and functional food studies.

Drug development today needs to balance agility, speed, and risk in defining probability of success for molecules, mechanisms, and therapeutic concepts. New techniques such as fMRI promise to be part of a sequence that could transform drug development. Although numerous review articles exist that discuss the use of imaging in drug development, no one source is available that combines the various techniques and includes a discussion of disease mapping.

Imaging in CNS Drug Discovery and Development, Implications for Disease and Therapy will serve to distill the most salient developments in the use of imaging in drug development and disease mapping. It will launch evolving concepts that integrate new imaging technologies and paradigms with molecular medicine and molecular profiling ("monics") as well as consider the ethical issues that arise as a result of disease or state diagnosis and the use of imaging in the public eye.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

In this volume of Reviews of Physiology, Biochemistry and Pharmacology there a contributions by M.D. Swope, E. Lolis, F.Hofmann, L. Lacinova, N. Klugbauer, M. Hermann, P. Berger, S.S. Shen, J.S. Kim, M.E. Weksler, M. Hirsch-Kauffmann and M.Schweiger.

"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.